Genome-wide screening identifies a KCNIP1 copy number variant as a genetic predictor for atrial fibrillation

Nature Communications
Chia-Ti TsaiJiunn-Lee Lin

Abstract

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Previous genome-wide association studies had identified single-nucleotide polymorphisms in several genomic regions to be associated with AF. In human genome, copy number variations (CNVs) are known to contribute to disease susceptibility. Using a genome-wide multistage approach to identify AF susceptibility CNVs, we here show a common 4,470-bp diallelic CNV in the first intron of potassium interacting channel 1 gene (KCNIP1) is strongly associated with AF in Taiwanese populations (odds ratio=2.27 for insertion allele; P=6.23 × 10(-24)). KCNIP1 insertion is associated with higher KCNIP1 mRNA expression. KCNIP1-encoded protein potassium interacting channel 1 (KCHIP1) is physically associated with potassium Kv channels and modulates atrial transient outward current in cardiac myocytes. Overexpression of KCNIP1 results in inducible AF in zebrafish. In conclusions, a common CNV in KCNIP1 gene is a genetic predictor of AF risk possibly pointing to a functional pathway.

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Citations

Feb 9, 2017·Current Opinion in Cardiology·Alexandra Pérez-SerraRamon Brugada
May 5, 2017·Physiological Reviews·Philipp GutRima Arnaout
Jul 22, 2016·Medicine·Chih-Chieh YuJiunn-Lee Lin
Mar 13, 2019·Journal of Clinical Medicine·Chia-Shan HsiehChia-Ti Tsai
Mar 3, 2019·Biomedicines·Panagiota Giardoglou, Dimitris Beis
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Mar 9, 2021·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Julieta LazarteJason D Roberts
Apr 20, 2021·PloS One·John W ColeCaspar Grond-Ginsbach
Apr 23, 2021·Journal of Molecular and Cellular Cardiology·Jesus VictorinoMiguel Manzanares

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Methods Mentioned

BETA
chip
genotyping
transfection
PCR
Assay
antisense oligonucleotide
electrophoresis

Software Mentioned

PARTEK Genomic Suite
ABI
R Project for Statistical Computing
R

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